Fibrinogen-like protein 1 is a major immune inhibitory ligand of LAG3
By Jun Wang, M. Sanmamed, I. Datar, T. T. Su, L. Ji, Jingwei Sun, Ling Chen, Yusheng Chen, G. Zhu, Weiwei Yin and 11 more. Cell, 2018
765 citations recorded by the source corpus.
SUMMARY Lymphocyte-activation gene 3 (LAG3) is an immune inhibitory receptor, with major histocompatibility complex class II (MHC-II) as a canonical ligand. However, it remains controversial whether MHC-II is solely responsible for the inhibitory function of LAG3. Here, we demonstrate that fibrinogen-like protein 1 (FGL1), a liver-secreted protein, is a major LAG3 functional ligand independent from MHC-II. FGL1 inhibits antigen-specific T-cell activation and ablation of FGL1 in mice promotes T-cell immunity. Blockade of the FGL1/LAG3 interaction by monoclonal antibodies stimulates tumor immunity and is therapeutic against established mouse tumors in a receptor-ligand inter-dependent manner. FGL1 is highly produced by human cancer cells and elevated FGL1 in the plasma of cancer patients is associated with a poor prognosis and resistance to anti-PD-1/B7-H1 therapy. Our findings reveal an immune evasion mechanism and have implications for the design of cancer immunotherapy.
Subfields: Immunology, Oncology
View Paper: https://www.semanticscholar.org/paper/bc11a90db4bbb33626437336f1f5a1a48853841a
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Citations in the corpus
- Novel immune checkpoint targets: moving beyond PD-1 and CTLA-4 (2019, background): “More recently, Wang and his co-workers elucidated that fibrinogen-like protein 1 (FGL1) was a novel high-affinity ligand for LAG-3 independent from MHC-II [58].”
- Advances in immunotherapy for hepatocellular carcinoma (2021, background): “I.M. receives funding from MINECO SAF2014-52361-R and SAF 2017- 83267-C2-1R; Worldwide Cancer Research Grant (15-1146); the Asociacion Española Contra el Cancer (AECC) Foundation under grant GCB15152947MELE; and the European Union’s Horizon 2020 Program (grant agreement no. 635122 PROCROP).”